Collaboration on cancer in fish may offer insights into the disease in humans

Scientists at the Centre for Environment, Fisheries & Aquaculture Science (Cefas) and from the Cancer Research UK (CRUK) Institute for Cancer Studies at the University of Birmingham are working together by using leading-edge techniques on fish that may help develop new ways of diagnosing and potentially treating liver cancer in humans.

As part of the National Marine Monitoring Programme (NMMP), Cefas scientists have noted high numbers of tumours (up to 14%) in dab and flounder sampled from sites in the open sea and some industrial estuaries. These tumours show clear similarities with human liver cancer. Their presence made scientists ask: ‘What are the environmental stressors that cause such high numbers?’ To help them to find an answer they are applying new technologies such as ‘proteomic’ techniques – hailed as the next frontier in molecular biology.

Proteomics enables researchers to compare the thousands of proteins found in cancer tissue to those found in normal tissue. Particular ‘stressors’ on organisms in a range of environments can be investigated (a stressor might be chemical, physical or biological). Potentially, this will lead to the identification of ‘protein profiles’ that are characteristic of particular stressors. These protein profiles or ‘biomarkers’ can be measured to pinpoint the specific causes within the environment (e.g. exposure to endocrine-disrupting chemicals, mixtures or single compounds) that might be responsible for changes in the tissue.

In the current Cefas study, scientists are using proteomics to investigate liver tumours of flatfish in the hope of discovering protein biomarkers indicative of cancer. They also hope to show that changes occurring during cancer development in fish and other animals will potentially be directly comparable with those occurring in humans.

Cefas scientist, Dr Grant Stentiford, said: ‘These new technologies are being used to gain a better understanding of human diseases such as cancer and are now opening up a whole new arena of opportunity for the study of disease in fish. By combining our findings, medical and environmental scientists can make great advances in discovering the changes occurring during cancer formation and, perhaps, also in treating the disease once it has formed.’

Proteomics provides more than a new suite of tools for environmental managers. It enables a new approach to the health assessment of animals. More than half of the 50,000 living vertebrate species are fish, and the occurrence of liver tumours in certain fish species appear to be associated with exposure to environmental carcinogens linked to pollution. In addition, fish tumours are very similar to those that occur in higher animals. That is why fish have gained an increasing amount of attention over the past 30 years as useful models for cancer research.

In the human arena, proteomics may enable researchers to predict response to treatment rather than just confirm disease, and to construct a systematic way to discover new targets for anti-cancer therapy. Potentially, scientists may be able to create bespoke therapies that locate and inactivate causative target proteins in the cancer of individuals. Such a ‘personalised’ approach could bring hope to a vast number of cancer patients. Indeed, ‘personalised medicine’ is a method already being used to treat chronic leukaemia and breast cancer.

Cefas scientists are collaborating with experts from the CRUK’s Institute of Cancer Studies at the University of Birmingham because of the apparent similarity between the liver cancers present in the fish collected under the NMMP and those appearing in humans. By observing the protein changes occurring within these cancers, it may be possible to identify common biomarkers. Eventually, it is hoped that blood plasma samples screened from the fish may be used to identify early-stage cancers, an approach also being pursued in human cancer research. Scientists also hope to gain a greater understanding of cancer progression in fish living in the wild.

Professor Philip Johnson from the CRUK’s Institute of Cancer Studies said: ‘Research into the causes of human cancer has been enhanced by the study of closely analogous, naturally occurring cancers in animals. Collaboration between research workers studying human and fish cancers holds great promise for increasing our understanding of the relationship between environmental toxins and liver cancer in man.’

Notes to editors

1. Cefas is an internationally renowned scientific research and advisory establishment, based at Lowestoft since 1902. It also has facilities at Weymouth, Burnham-on-Crouch and Whitehaven. It became an executive agency of the Department for Environment, Food and Rural Affairs in 1997.  
2. Cefas undertakes work on fisheries management, environmental protection and aquaculture. It offers a wide range of research, advisory, consultancy, monitoring and training activities to government departments (UK and foreign, central and local), international agencies, commercial companies and aid organisations.
3. Dab (Limanda limanda) and flounder (Platichthys flesus) are both flat fish species, found respectively offshore and in estuaries. As both species eat seabed (‘benthic’) creatures, they are more likely to be exposed to concentrated levels of environmental contaminants found in the sediment , which bio-accumulate in the liver. The liver is the main organ for detoxification, hence its importance when searching for environmental effects.  
4. Several fish species have been identified as potential models for cancer study. Due to their low cost, portability, ease of husbandry, relatively short lifecycles and advancements in genome typing, fish may provide useful alternatives to mammals for use in cancer research. Certain fish models exhibit specific tumour types that eventually could be used to study specific carcinogenic pathways in humans.  
5. Whereas traditional histology (comparing thin slices of stained tissue under a microscope) has advanced the understanding of the cancer process, it does not tell the whole story. ‘Proteomics’ is the study of protein components in cells, tissue or whole organisms. Proteins play a key role in intercellular signalling and in the immune system. As such they are the interface between the cell and its environment, and between disease and normal tissue. Protein over- or under-expression is the cause and effect of diseases such as cancer. These expression changes are led by similar over- and under-expression of the genes that make them.  
6. Potential chemical 'stressors' include organic compounds such as polycyclic aromatic hydrocarbons (PAH). There is evidence that links PAH exposure to the presence of liver disease in bottom-living fish. Physical stressors include environmental changes such as temperature, salinity and oxygen levels in the water. Biological stressors can be extremely varied, and could include disease agents such as parasites, bacteria and viruses; population density and food availability; spawning activity, etc.  
7. For more information about the work of Cancer Research UK see http://www.cancerresearchuk.org/.  
8. Cefas scientists are available for interview, and digital photographs can be supplied on request. Please contact the Cefas press office.

Press contact: Anne McClarnon 01502 524370 (mobile: 0776 829 0938) / anne.mcclarnon@cefas.co.uk